Summary

Commonly reported side effects of anakinra include: infection, antibody development, and inflammation at injection site. Other side effects include: neutropenia. Continue reading for a comprehensive list of adverse effects.

Applies to anakinra: subcutaneous solution.

Serious side effects of Anakinra

Along with its needed effects, anakinra may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking anakinra:

More common

• Agitation
• coma
• confusion
• decreased urine output
• diarrhea
• dizziness
• fast heartbeat
• fever or chills
• headache
• itching, pain, redness, swelling, tenderness or warmth on the skin
• irritability
• joint pain
• lethargy
• muscle aches, pains, and twitching
• nausea or vomiting
• nervousness
• numbness or tingling in the hands, feet, or lips
• restlessness
• runny nose or sneezing
• seizures
• sore throat
• stomach pain
• stupor
• swelling of the face, ankles, or hands
• swelling of the feet or lower legs
• trouble breathing
• unusual tiredness or weakness
• weakness or heaviness of the legs

Less common

• Black, tarry stools
• cough
• difficulty with swallowing
• hives, itching, or rash
• painful or difficult urination
• pale skin
• swelling of the face or lips
• ulcers, sores, or white spots in the mouth
• unusual bruising or bleeding

Incidence not known

• Bleeding gums
• blood in the urine or stools
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips or tongue

Other side effects of Anakinra

Some side effects of anakinra may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• difficulty with moving
• headache
• muscle aches or stiffness

For Healthcare Professionals

Applies to anakinra: subcutaneous solution.

General

The most common side effects reported in patients with rheumatoid arthritis (RA) were injection site reaction, worsening of RA, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, influenza-like symptoms, and abdominal pain. The most common side effects reported in patients with neonatal-onset multisystem inflammatory disease (NOMID) during the first 6 months of therapy were injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis; the most common side effects after the first 6 months of therapy included arthralgia, headache, pyrexia, upper respiratory tract infections, nasopharyngitis, and rash. The most common side effects reported in patients with deficiency of interleukin-1 receptor antagonist (DIRA) were upper respiratory tract infections, rash, pyrexia, influenza-like illness, and gastroenteritis.^[Ref]

Cardiovascular

Common (1% to 10%): Hypertension

Dermatologic

Common (1% to 10%): Ecchymosis, rash (including maculopapular rash, urticarial rash), pruritus

Gastrointestinal

Very common (10% or more): Vomiting (up to 14%)

Common (1% to 10%): Nausea, diarrhea, abdominal pain, dyspepsia

Frequency not reported: Gastroenteritis

Genitourinary

Common (1% to 10%): Urinary tract infection

Hematologic

In controlled trials, decreases in total WBC counts of at least 1 WHO toxicity grade occurred in 8% of patients treated with this drug, compared with 2% of placebo-treated patients. Neutropenia (absolute neutrophil count [ANC] less than 1 x 10[9]/L) developed in 0.4% of patients treated with this drug. Increases in eosinophil differential percentage of at least 1 WHO toxicity grade occurred in 9% of patients treated with this drug, compared with 3% of placebo-treated patients. Of patients treated concurrently with this drug and etanercept, 2% developed neutropenia (ANC less than 1 x 10[9]/L). While neutropenic, 1 patient developed cellulitis which recovered with antibiotic therapy. Decreases in platelets (WHO toxicity grade 1) occurred in 2% of patients treated with this drug, compared with 0% of placebo-treated patients.

During postmarketing experience, thrombocytopenia has been reported, including occasional case reports indicating severe thrombocytopenia (i.e., platelet counts less than 10 x 10[9]/L).

Common (1% to 10%): Neutropenia, thrombocytopenia, decreased total WBC count, decreased platelets, increased eosinophil differential percentage

Postmarketing reports: Thrombocytopenia (including severe thrombocytopenia)

Hepatic

Uncommon (0.1% to 1%): Hepatic enzyme increased

Postmarketing reports: Noninfectious hepatitis, elevations of transaminases

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reactions (including anaphylactic reactions, angioedema, urticaria, pruritus)

Immunologic

Very common (10% or more): Antidrug antibodies positive (up to 49%)

Common (1% to 10%): Neutralizing antibodies positive

Postmarketing reports: Macrophage activation syndrome

Local

The most common and consistently reported therapy-related side effect associated with this drug was injection site reaction (characterized by erythema, ecchymosis, inflammation and/or pain). In general, injection site reactions were reported within the first 2 to 4 weeks of therapy and lasted for 2 to 6 weeks. Injection site reactions were reported as mild, moderate, and severe in 72.6%, 24.1%, and 3.2% of patients, respectively.

Very common (10% or more): Injection site reaction (including erythema, ecchymosis, inflammation, pain; up to 71.2%)

Musculoskeletal

Very common (10% or more): Worsening of RA (up to 19.1%), arthralgia (up to 11.6%)

Common (1% to 10%): Limb pain, back pain, myalgia, fracture

Nervous system

Very common (10% or more): Headache (up to 14%)

Common (1% to 10%): Dizziness

Oncologic

Frequency not reported: Lymphomas, malignancies (including breast, respiratory system, digestive system)

Other

In clinical trials during the first 6 months of therapy, infection was reported in 39% of patients treated with this drug and 37% of patients treated with placebo. Over 6 and 12 months, respectively, serious infections were reported in 2% and 3% of patients treated with this drug and 1% and 2% of placebo-treated patients; these infections were primarily bacterial (e.g., cellulitis, pneumonia, bone and joint infections). Most patients (73%) continued on study drug after the infection resolved. No serious opportunistic infections were reported. Patients with asthma were at higher risk of developing serious infection when treated with this drug (8 of 177 patients [4.5%]) compared to placebo (0 of 50 patients [0%]).

In extension trials, the overall rate of serious infection was stable over time and comparable to that observed in controlled trials. In clinical trials and postmarketing experience, cases of opportunistic infections were reported and included fungal, mycobacterial, viral, and bacterial pathogens. Infections have been observed in all organ systems and have been reported with this drug alone or in combination with immunosuppressive agents.

Serious infections were reported in 7% of patients treated with this drug and etanercept for up to 24 weeks. The most common infections were bacterial pneumonia (4 cases) and cellulitis (4 cases); 1 patient with pulmonary fibrosis and pneumonia died due to respiratory failure.

In 2 long-term safety studies of RA over 3 years, 4 deaths due to serious infections (1 pneumonia and 3 sepsis) were reported; these deaths were considered related to this drug.

Very common (10% or more): Infection (up to 39%), pyrexia (up to 11.6%), increased blood cholesterol

Common (1% to 10%): Influenza-like symptoms, peripheral edema, injury, fever, chest pain, fatigue, serious infections (primarily bacterial [e.g., cellulitis, pneumonia, bone and joint infections, sepsis])

Frequency not reported: Death

Psychiatric

Common (1% to 10%): Insomnia, depression

Respiratory

Very common (10% or more): Upper respiratory tract infection (up to 14%), nasopharyngitis (up to 11.6%)

Common (1% to 10%): Sinusitis, bronchitis, cough, sore throat, upper respiratory tract congestion, dyspnea